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Phosphorylation of the acidic domain of Mdm2 by protein kinase CK2

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Abstract

The Murine double-minute clone 2 (Mdm2) onco-protein is the principal regulator of the tumour suppressor, p53. Mdm2 acts as an E3-type ubiquitin ligase that mediates the ubiquitylation and turnover of p53 under normal, unstressed circumstances. In response to cellular stress, such as DNA damage, the Mdm2–p53 interaction is disrupted. Part of the mechanism of uncoupling p53 from Mdm2-mediated degradation involves hypo-phosphorylation of a cluster of phosphorylated serine residues in the central acidic domain of Mdm2. Here, we show that two of the residues within this domain that are phosphorylated in vivo, Ser-260 and Ser-269, are phosphorylated by CK2 in vitro. Treatment of cells with the CK2 inhibitor, 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), leads to the induction of p53 and downstream targets of p53 including Mdm2 itself and p21. These data are consistent with the idea that CK2-mediated phosphorylation of Mdm2 may regulate Mdm2-mediated p53 turnover.

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Authors and Affiliations

  1. Molecular Signalling Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

    Nerea Allende-Vega, Sylvia Dias, Diane Milne & David Meek

  2. Molecular Signalling Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, U.K.

    David Meek

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  1. Nerea Allende-Vega
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  2. Sylvia Dias
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  3. Diane Milne
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  4. David Meek
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Correspondence to David Meek.

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Allende-Vega, N., Dias, S., Milne, D. et al. Phosphorylation of the acidic domain of Mdm2 by protein kinase CK2. Mol Cell Biochem 274, 85–90 (2005). https://doi.org/10.1007/s11010-005-3074-4

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  • DOI: https://doi.org/10.1007/s11010-005-3074-4

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